Rational and combinatorial strategies for designing oligonucleotides targeted to RNA structures.
Many RNA structures play a key role in the regulation of gene expression. We designed synthetic oligonucleotides able to interact with folded RNA regions (see Toulmé et al., Biochimie (1996) 78, 663-673, for a review). We have demonstrated that a decanucleotide can form a triple helix with the stem of the hairpin responsible for ribosomal frame-shifting of the gag-pro message of HTLV-I, leading to the inhibition of translation. We have isolated, through an in vitro selection procedure, from a library composed of oligonucleotides with a random part of 30 nucleotides, sequences able to bind to the TAR RNA element of HIV-1 with a dissociation constant of 20-50 nM. The association between the two partners involve non-canonical interactions. This extends the range of potential targets for antisense sequences to functional RNA structures.
Toulmé
J J
JJ
INSERM U386, IFR Pathologies Infectieuses, Université Victor Segalen, Bordeaux, France.
Le Tinévez
R
R
Boiziau
C
C
Dausse
E
E
D015195:Drug Design; D015723:Gene Library; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000378:metabolism; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism
D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D012367:RNA, Viral; D012313:RNA